L'entrée des cellules en mitose se caractérise par l'augmentation d'expression de la kinase Aurora A. Nous avons caractérisé l'effet du sn38, métabolite actif de l'irinotecan utilisé dans le traitement du cancer colorectal sur l'expression de cette kinase. En absence de traitement, le facteur de transcription c-myc se lie au promoteur d'Aurora A et l'active. Cependant, le traitement des cellules avec du sn38 induit l'inhibition de c-myc et son absence du promoteur d'Aurora A s'accompagnant de l'induction du processus de sénescence. Nous avons également étudié l'effet de l'oncogène Ras sur la kinase Aurora A. Cet oncogène induit une diminution d'expression d'Aurora A par une modulation de l'activité des cofacteurs transcriptionnels de c-myc. En résumé, nos résultats indiquent qu' Aurora A est une cible des traitements de chimiothérapie et des mécanismes de contrôles oncogéniques. Le blocage de son expression constitue certainement une protection contre le développement tumoral.

<p>The Auroral Large Imaging System (ALIS) was proposed in 1989 by Åke Steen as a joint Scandinavian ground-based nework of automated auroral imaging stations. The primary scientic objective was in the field of auroral physics, but it was soon realised that ALIS could be used in other fields, for example, studies of Polar Stratospheric Clouds (PSC), meteors, as well as other atmospheric phenomena.</p><p>This report describes the design, operation and scientic results from a Swedish prototype of ALIS consisting of six unmanned remote-controlled stations located in a grid of about 50 km in northern Sweden. Each station is equipped with a sensitive high-resolution (1024 x 1024 pixels) unintensified monochromatic CCDimager. A six-position filter-wheel for narrow-band interference filters facilitates absolute spectroscopic measurements of, for example, auroral and airglow emissions. Overlapping fields-of-view resulting from the station baseline of about 50 km combined with the station field-of-view of 50° to 60°, enable triangulation as well as tomographic methods to be employed for obtaining altitude information of the observed phenomena.</p><p>ALIS was probably one of the first instruments to take advantage of unintensi- fied (i.e. no image-intensifier) scientific-grade CCDs as detectors for spectroscopic imaging studies with multiple stations of faint phenomena such as aurora, airglow, etc. This makes absolute calibration a task that is as important as it is dificult.</p><p>Although ALIS was primarily designed for auroral studies, the majority of the scientific results so far have, quite unexpectedly, been obtained from observations of HF pump-enhanced airglow (recently renamed Radio-Induced Aurora). ALIS made the first unambiguous observation of this phenomena at high-latitudes and the first tomography-like inversion of height profiles of the airglow regions. The scientific results so far include tomographic estimates of the auroral electron spectra, coordinated observations with satellite and radar, as well as studies of polar stratospheric clouds. An ALIS imager also participated in a joint project that produced the first ground-based daytime auroral images. Recently ALIS made spectroscopic observations of a Leonid meteor-trail and preliminary analysis indicates the possible detection of water in the Leonid.</p>

The Auroral Large Imaging System (ALIS) was proposed in 1989 by Åke Steen as a joint Scandinavian ground-based nework of automated auroral imaging stations. The primary scientic objective was in the field of auroral physics, but it was soon realised that ALIS could be used in other fields, for example, studies of Polar Stratospheric Clouds (PSC), meteors, as well as other atmospheric phenomena. This report describes the design, operation and scientic results from a Swedish prototype of ALIS consisting of six unmanned remote-controlled stations located in a grid of about 50 km in northern Sweden. Each station is equipped with a sensitive high-resolution (1024 x 1024 pixels) unintensified monochromatic CCDimager. A six-position filter-wheel for narrow-band interference filters facilitates absolute spectroscopic measurements of, for example, auroral and airglow emissions. Overlapping fields-of-view resulting from the station baseline of about 50 km combined with the station field-of-view of 50° to 60°, enable triangulation as well as tomographic methods to be employed for obtaining altitude information of the observed phenomena. ALIS was probably one of the first instruments to take advantage of unintensi- fied (i.e. no image-intensifier) scientific-grade CCDs as detectors for spectroscopic imaging studies with multiple stations of faint phenomena such as aurora, airglow, etc. This makes absolute calibration a task that is as important as it is dificult. Although ALIS was primarily designed for auroral studies, the majority of the scientific results so far have, quite unexpectedly, been obtained from observations of HF pump-enhanced airglow (recently renamed Radio-Induced Aurora). ALIS made the first unambiguous observation of this phenomena at high-latitudes and the first tomography-like inversion of height profiles of the airglow regions. The scientific results so far include tomographic estimates of the auroral electron spectra, coordinated observations with satellite and radar, as well as studies of polar stratospheric clouds. An ALIS imager also participated in a joint project that produced the first ground-based daytime auroral images. Recently ALIS made spectroscopic observations of a Leonid meteor-trail and preliminary analysis indicates the possible detection of water in the Leonid.

The Sli15-Ipl1-Bir1 chromosomal passenger complex is essential for proper kinetochore-microtubule attachment and spindle stability in the budding yeast Saccharomyces cerevisiae. Subcellular localization of this complex during anaphase is regulated by the Cdc14 protein phosphatase, which is kept inactive in the nucleolus until anaphase onset. I show here that the predominantly nucleolar ribosome biogenesis protein Utp7 is also present at kinetochores and is required for normal organization of kinetochore proteins and proper chromosome segregation. Utp7 associates with and regulates the localization of Sli15 and Cdc14. It prevents the abnormal localization of Sli15 on cytoplasmic microtubules, the premature concentration of Sli15 on the pre-anaphase spindle, and the premature nucleolar release of Cdc14 before anaphase onset. Utp7 regulates Sli15 localization not entirely through its effect on Cdc14. Furthermore, the mitotic exit block caused by Cdc14 inactivation is relieved partially by the simultaneous inactivation of Utp7. Thus, Utp7 is a multifunctional protein that plays essential roles in the vital cellular processes of ribosome biogenesis, chromosome segregation and cell cycle control. Protein phosphatase 1, Glc7 opposes in vivo functions of the Ipl1-Sli15-Bir1 kinase complex in budding yeast. I show here Scd5- a targeting subunit of Glc7 that regulates endocytosis/cortical actin organization and undergoes nuclear-cytoplasmic shuttling- is present at kinetochores. Ipl1 associates with both Glc7 and Scd5. The scd5-PP1[Delta]2 mutation, which disrupts the association between Glc7 and Scd5, also disrupts the association between Ipl1 and Scd5-Glc7 without affecting the kinetochore localization of these proteins. Genetic studies suggest that Scd5 may positively regulate both Glc7 phosphatase and the Ipl1 kinase complex. In accordance, Scd5 stimulates in vitro kinase activity of Ipl1. scd5-PP1[Delta]2 cells missegregate chromosomes severely due to several defects: i) at least one of sister kinetochores appears not attached to microtubule. ii) sister chromatids are persistently cohesed through anaphase. iii) Sli15 is hyperphosphorylated and less abundant on the anaphase spindle resulting in unstable mitotic spindle. These results together suggest that Scd5 functions in diverse processes that are essential for faithful chromosome segregation. How Scd5 coordinately regulates two apparently antagonistic enzymatic activities of Ipl1 and Glc7 remains to be determined. / text

This dissertation critically examines why mid-Victorian fiction often dismisses or complicates monetary transactions and monetary charity, even as it negatively portrays differences in social status and wealth. I argue that the novel uses representations of failed charity to reconstruct, however briefly, a non- monetary and non-economic source of value. Further, I examine how the novel uses techniques of both genre and style to predict, form, and critique alternate, non-economic, social models. While tension surrounding the practice of charity arises in the late eighteenth century, the increasing dominance of political economy in public discourse forced Victorian literature to take a strong stance, for reasons of both ethics and genre. This stance is complicated by the eighteenth-century legacy that sees charity as a kind of luxury. If giving to the poor makes us feel good, this logic suggests, surely it isn’t moral. Thus, while much eighteenth- and nineteenth-century literature remains dedicated to the ethics of charity, the practice becomes immensely complex. By discussing the works of Tobias Smollett, Charles Dickens, Elizabeth Barrett Browning, and George Eliot, this project exposes a wide variety of responses to this deep cultural anxiety. These authors are, ultimately, strongly invested in redefining the meaning of benevolence as a valid form of social action by moving that benevolence away from monetary gifts and toward abstractly correct moral feelings, though their individual solutions vary widely. / text

La kinase Aurora B appartient au complexe des protéines passagères. Ce complexe est impliqué dans la régulation de la condensation, constriction et ségrégation des chromosomes, ainsi que dans la cytokinèse. Son rôle est donc crucial pour prévenir la formation de cellules cancéreuses. Cependant, l'étude de la fonction précise d'Aurora B dans chacune des phases de la mitose est limitée par la durée de celle-ci, et par le manque de spécificité des inhibiteurs existants. Nous avons donc développé une stratégie basée sur la photo-inactivation de la kinase par le chromophore Killer-Red, fusionné à la protéine. L'émission locale de ROS après irradiation, permet alors la photo-inactivation spécifique et temporelle d'Aurora B. La photo-inactivation d'Aurora B avant anaphase aboutie soit à un arrêt de la mitose, soit à la régression du sillon de division, provoquée par l'entrée en anaphase en présence de chromosomes retardés. La photo-inactivation d'Aurora B en début d'anaphase a pour conséquence la régression du sillon de division en cytokinèse ; apportant la première indication directe de l'implication d'Aurora B dans le fuseau mitotique en cytodiérèse. De façon surprenante, la photo-inactivation de la kinase au niveau du corps résiduel, après constriction du sillon de division, n'affecte pas l'abscission. La photo-inactivation d'Aurora B n'affecte pas la localisation des autres membres du complexe des protéines passagères, indiquant que la kinase n'est pas impliquée dans la dynamique du complexe. Les résultats obtenus montrent sans aucun doute l'implication d'Aurora B dans chacune des phases de la mitose, suggérant que la phosphorylation par Aurora B de ses substrats permet le controle de la division cellulaire.

Aurora A (AurA) is an important mitotic kinase mainly studied for its involvement in cell cycle progression, centrosome maturation, mitotic spindle pole organization and bipolar spindle formation. It localizes to duplicated centrosomes and spindle microtubules (MTs) during mitosis where it regulates various factors participating in metaphase spindle formation. AurA is degraded late in mitosis suggesting that it might also have a function in anaphase. In this study we focused in understanding AurA function during anaphase in two different experimental systems. First, we kept AurA active in cycled Xenopus egg extracts and found that MTs maintained their mitotic organization longer throughout mitotic exit. We also observed chromosome segregation defects and problematic nuclear envelope formation. These observations indicate that AurA activity needs to be down-regulated for the transition from metaphase back to interphase. To get insights into the role of AurA during metaphase-anaphase transition we initially asked whether its kinase activity is still necessary for the maintenance of the metaphase spindle. We saw that the inhibition of AurA kinase activity in metaphase resulted to a collapse of the established metaphase spindle in HeLa cells. Indicating that AurA activity is necessary for the metaphase spindle maintenance. Then, we looked whether AurA kinase activity is still necessary during anaphase. We inhibited AurA at the onset of anaphase in Hela cells and found that anaphase spindles were smaller. We also observed that the MT structure responsible for anaphase spindle elongation, the central spindle, was defectively assembled and organized. Moreover, in cells where AurA was inhibited segregation of chromosomes was defective. These results indicate that AurA kinase activity is necessary for anaphase spindle elongation, central spindle assembly and organization and chromosome segregation. To understand further how AurA regulates anaphase spindle formation we looked known AurA substrates. We depleted TACC3, a known AurA substrate involved in MT formation earlier in mitosis and observed that TACC3 depletion phenocopied AurA inhibition. This indicates that TACC3 has a function in MT organization and chromosome segregation during anaphase and this function could possibly be regulated by AurA. In this study we have demonstrated that AurA activity is essential for metaphase spindle maintenance. We also found that during anaphase when AurA is either maintained active or inhibited MT organization is greatly affected and chromosome segregation is defective. Suggesting that AurA activity needs to be tightly controlled during anaphase for a correct completion of mitosis. / Aurora A (AurA) es una quinasa mitótica importante que se ha estudiado principalmente en su papel durante la progresión del ciclo celular, la maduración del centrosoma, la organización y la formación del polo y del huso mitótico. Durante la mitosis, AurA se localiza en los centrosomas duplicados y en los microtúbulos (MTs) del huso y se ha observado que regula varios factores que participan en la formación del huso mitótico. AurA se degrada al final de la mitosis indicando que pueda tener una función durante la anafase. En este estudio nos hemos centrado en la comprensión de la función de AurA durante la anafase en dos sistemas experimentales diferentes. En primer lugar, utilizando extractos de huevos de Xenopus hemos mantenido AurA activa durante la transición de metafase a anafase y hemos visto que los MTs del huso mitótico mantienen su organización durante más tiempo. También hemos observado que cuando AurA se mantiene activa existen defectos en la segregación cromosómica y la formación de la membrana nuclear. Esto indica que la actividad de AurA tiene un papel regulador sobre los MTs y la chromatina durante la transición de la metafase a la interfase. Para entender cual es la función de AurA durante la transición de metafase a anafase primero hemos estudiado si la actividad de la quinasa es necesaria para el mantenimiento del huso mitótico. Hemos visto que la inhibición de la actividad quinasa AurA resultó en el colapso del huso durante la metafase en células HeLa. Esto indica que la actividad de AurA es necesaria para el mantenimiento del huso mitótico de metafase. A continuación hemos analizamos si la actividad quinasa de AurA sigue siendo necesaria para la anafase. Para ello hemos inhibido AurA en células Hela al inicio de la anafase. En estas condiciones los husos de la anafase son más pequeños y la estructura de los MTs responsable del alargamiento del huso mitótico durante la anafase, el huso central, se organiza defectuosamente. Además, se encontraron errores durante la segregación de los cromosomas. Estos resultados indican que la actividad quinasa de AurA es necesaria para el alargamiento del huso durante la anafase y la organización y segregación cromosómica. Para entender el mecanismo de la función de AurA durante la anafase hemos estudiado a sustratos de AurA. Al estudiar TACC3 , un sustrato conocido de AurA que participa en la formación de MTs en las fase iniciales de la mitosis hemos encontrado que su eliminación de células HeLa produce el mismo fenotipo que la inhibición de AurA. Esto indica que TACC3 tiene una función en la organización de MT y la segregación de cromosomas durante la anafase y que esta función podría estar regulada por la quinasa AurA. En este estudio hemos demostrado que la actividad quinasa de AurA es esencial para el mantenimiento del huso mitótico. También hemos encontrado que durante la anafase cuando la quinasa AurA se mantiene activa o se inhibe la organización de los MTs del huso mitótico se ve muy afectada y los cromosomas se segregan defectuosamente. Por tanto los resultados de este estudio indican que la actividad quinasa de AurA está estrechamente controlada durante la anafase para el correcto cumplimiento de la mitosis.

Made available in DSpace on 2016-08-03T12:20:06Z (GMT). No. of bitstreams: 1 Jose Francisco Souza.pdf: 837694 bytes, checksum: 9efe38f44078b9ac327bb410323bbdb1 (MD5) Previous issue date: 2006-08-29 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / Esta dissertação procura aliar os novos pressupostos teóricos e metodológicos da Nova História Cultural ao estudo da religião a partir da atuação da Comunidade Evangélica Nova Aurora. Através do discurso religioso evangélico e do oferecimento de recursos básicos, CENA tem como um de seus principais objetivos recuperar pessoas excluídas e marginalizadas que vivem em ambientes precários e principalmente nas ruas do centro velho da capital paulista. O texto reconstrói o contexto e o cotidiano do projeto, intentando captar sua história através das múltiplas percepções dos sujeitos envolvidos. Pergunta também pelos deslocamentos que ocorrem no imaginário religioso, onsiderando-se a norma institucionalizada no campo protestante. Para compor a documentação deste trabalho, nos valemos dos métodos da história oral, colhendo depoimentos dos protagonistas desta realidade e expondo uma trajetória histórica da Comunidade a partir da memória religiosa de sujeitos normalmente esquecidos como atores históricos.(AU)

The conservation of aquatic-breeding amphibian populations and their habitats is increasingly challenged by urban and rural development, which is occurring more intensively and more rapidly than ever before. Some species are now impacted by development throughout their range. This has forced a re-evaluation of the potential of developed landscapes for providing habitat and contributing to regional conservation strategies. For many amphibians, little is known about the criteria necessary for persistence in a developed landscape. Considerable variation in the physiology, habitat requirements, and movement behaviour of amphibians suggests that responses to habitat loss, alteration, and fragmentation are species-specific. In this thesis, I investigate species-habitat relationships for the northern red-legged frog (Rana aurora) and the Pacific chorus frog (Pseudacris regilla) in a mixed urban-rural landscape in southwestern British Columbia to evaluate the potential for species persistence despite urban and rural development throughout their range. I used repeat auditory surveys of the species’ breeding chorus to determine presence or absence at potential breeding wetlands. I then related species occurrence and abundance to characteristics of the aquatic and terrestrial environment measured at multiple spatial scales. Both species were found to use rural and urban wetlands, though R. aurora were rarely detected while P. regilla were common. Occurrence was best explained by characteristics of the terrestrial environment, rather than within-wetland characteristics, though influential terrestrial characteristics and their scale of impact differed between species. Within the context of the developed landscape, I identify species-specific positive and negative habitat associations and suggest the spatial scales at which management of these habitat characteristics will be most effective. These criteria may help to explain the species’ current distribution, prioritize management strategies, predict the effectiveness of habitat conservation and restoration projects, and inform development in municipalities seeking to maintain or enhance amphibian diversity. / Graduate / 2019-09-11

Submitted by Erika Demachki (erikademachki@gmail.com) on 2015-01-29T17:17:40Z No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Tese - Sebastião Antônio Mendanha Neto - 2014.pdf: 7092471 bytes, checksum: 12e06f6af9661e3416fd2248ee25333c (MD5) / Approved for entry into archive by Erika Demachki (erikademachki@gmail.com) on 2015-01-29T17:41:44Z (GMT) No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Tese - Sebastião Antônio Mendanha Neto - 2014.pdf: 7092471 bytes, checksum: 12e06f6af9661e3416fd2248ee25333c (MD5) / Made available in DSpace on 2015-01-29T17:41:44Z (GMT). No. of bitstreams: 2 license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Tese - Sebastião Antônio Mendanha Neto - 2014.pdf: 7092471 bytes, checksum: 12e06f6af9661e3416fd2248ee25333c (MD5) Previous issue date: 2014-04-25 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The interactions of terpenes with membranes of erythrocyte, fibroblasts, stratum corneum and the model membranes of 1,2-dipalmitoylsn -glycero-3-phosphocholine were investigated by using the the electron paramagnetic resonance and fluorescence spectroscopic of lipophilic probes. It has been shown that when added at high concentrations to systems having a high lipid/solvent ratio, terpenes such as 1,8-cineol, α-terpineol, (+)-limonene and nerolidol are able to self-stabilize in molecular aggregates which can extract the bilayers lipids. Studies on the hemolytic and cytotoxic potential of various terpenes showed that cell damage caused by these molecules are concentration dependent and that among the studied terpenes, nerolidol and α-terpineol are the most hemolytic and cytotoxic, while (+)-limonene and 1,8-cineole are the least hemolytic and cytotoxic. However, the low correlation between these two tests indicates that the processes involved in each case are not completely dependent. It was also shown that once embedded in the membrane, terpenes increase the fluidity of lipid bilayers and decrease the temperature of the main phase transition. Differences between increased fluidity promoted by sesquiterpene nerolidol and all monoterpenes studied were observed. Meanwhile, in a comparison of the effect of the monoterpenes studied, no significant differences in their ability to increase membrane fluidity were detected. Furthermore, it was demonstrated by using confocal and atomic force microscopy and fluorescence spectroscopy that the 1,2-distearoylsn -glycero-3-(Aurora nanoparticles) is better incorporated in lipid membranes under fluid phase and that the addition of 0.1% of these conjugated nanoparticles do not produces large variations in membrane fluidity and no causes substantial morphological changes of lipid bilayers. / As intera¸c˜oes de terpenos com membranas de eritr´ocito, fibroblastos, estrato c´orneo e membrana modelo composta de 1,2-dipalmitoil-sn -glicero-3-fosfocolina foram investigadas por meio das espectroscopias de ressonˆancia paramagn´etica eletrˆ onica e de fluorescˆencia por meio do uso de sondas lipof´ılicas. Foi poss´ıvel demonstrar que quando adicionados em altas concentra¸c˜oes `a sistemas que possuem uma alta rela¸c˜ao lip´ıdio/solvente, terpenos como o 1,8-cineol, α-terpineol, (+)-limoneno e nerolidol s˜ao capazes de se estabilizar em agregados moleculares capazes de extrair os lip´ıdios das bicamadas. Estudos sobre o potencial hemol´ıtico e citot´oxico de v´arios terpenos demostraram que os danos celulares causados por estas mol´eculas s˜ao dependentes da concentra¸c˜ao e que dentre os terpenos estudados, nerolidol e terpineol s˜ao os mais hemol´ıticos e citot´oxicos enquanto limoneno e cineol s˜ao os menos hemol´ıticos e citot´oxicos. Entretanto, a baixa correla¸c˜ao entre estes dois testes indica que os processos envolvidos em cada caso n˜ao s˜ao totalmente dependentes. Ficou demonstrado ainda que uma vez incorporados nas membranas, os terpenos aumentam a fluidez das bicamadas lip´ıdicas e diminuem a temperatura de sua transi¸c˜ao de fase principal. Diferen¸cas entre o aumento de fluidez promovido pelo sesquiterpeno nerolidol e por todos os monoterpenos estudados foram verificadas. Contudo, uma compara¸c˜ao entre o efeito dos monoterpenos estudados, n˜ao aponta para diferen¸cas significativas entre suas capacidades de aumento de fluidez. Al´em disso, foi demostrado atrav´es das microscopias confocal e de for¸ca atˆomica e da espectroscopia de fluorescˆencia que a 1,2-distearoil-sn -glicero-3-(Nanopart´ıculas Aurora) ´e melhor incorporada em membranas lip´ıdicas em fase fluida e que a adi¸c˜ao de 0,1% destas nanopart´ıculas conjugadas n˜ao produz grandes varia¸c˜oes na fluidez e n˜ao provoca mudan¸cas morfol´ogicas substanciais das bicamadas lip´ıdicas.